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Biomedical subjects

E Beretta

Publications and source records attributed to E Beretta.

13 recordsLinked to original sources
PubMed1979

Metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride in rat urine.

In 24 hr urine of rats orally given 150 mg/kg of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride (DL 150), no unchanged compound was detected. Three metabolites, less polar than DL 150, were isolated, their structures assigned by UV, MS, IR and 1H NMR spectroscopies, and confirmed by synthesis. They are: 3-[bis-(2-hydroxyethyl)amino]-6-isopropoxypyridazine (1); 3-[bis-(2-hydroxyethyl)amino]pyridazine (2); 3-methyl-6-[bis-(2-hydroxyethyl)amino]-s-triazolo[4,3-b]pyridazine (3). The metabolism of DL 150 in the rat follows some of the metabolic pathways reported for hydralazine.

Animals↗
PubMed1978

Ultrastructure and function in sympathetic ganglia isolated from rats infected with pseudorabies virus.

(1) After inoculation of the pseudorabies virus in the anterior chamber of the eye of the rat, virions can be found only in the neurons of the superior cervical sympathetic ganglion and in the sensory ganglion of the fifth nerve on the inoculated side. Other nervous structures--central or peripheral--are not infected. (2) It is shown that the retrograde axonal flow carries the virus from the eye to the sympathetic neurons. (3) The ultrastructure of the infected neuron has been studied at various intervals after inoculation and at different stages of the viral replication. (4) Excised infected ganglia in vitro show a spontaneous electrophysiological activity that can be recorded on both the post- and preganglionic nerve. Such an activity has never been seen in normal excised ganglion of rat. (5) The shape and frequency of the electrophysiological discharges recorded on the postganglionic nerve have been analyzed at various intervals after inoculation. (6) Correlations established between the ultrastructure, the effect of various drugs and the electrophysiological activity permit the proposal of various hypothesis about the abnormal activity of the infected neurons.

Action Potentials↗
PubMed1977

Plasma levels and urinary elimination of diftalone, paracetamol, and their metabolites after single oral administration in man.

The plasma levels of diftalone, its metabolite 7-hydroxydiftalone, unconjugated and total paracetamol have been assessed in 6 healthy volunteers after oral administration of diftalone 0.75 g and of paracetamol 1.0 g, given alone and in combination in a cross-over fashion. In the same subject the urinary elimination of 7-hydroxydiftalone, and of unconjugated and total paracetamol has also been estimated. The results provide some indication of a slight increase in the plasma levels of unconjugated and total paracetamol, when the drug is administered in combination with diftalone. The increase, however, does not reach the significance level. As to diftalone and its metabolite, the differences between the plasma levels obtained after administration of the compound alone and those obtained when it was given in combination were negligible. Furthermore, the urinary recoveries of 7-hydroxydiftalone and of unconjugated and total paracetamol were very similar after administration of each compound alone and of their combination. It is concluded that the administration of single doses of diftalone and paracetamol in combination does not produce any pharmacokinetic interaction likely to be of clinical relevance.

Acetaminophen↗
PubMed1977

Influence of food intake on the absorption of diftalone in man.

An average 2.2-fold increase in the peak plasma concentrations of the non-steroidal anti-inflammatory agent diftalone in the presence of food was observed in three studies carried out with healthy volunteers who received an oral dose of 0.75 g (6 subjects, study 1), 0.25 g (10 subjects, study II) and 0.5 g (6 subjects, study V) of the compound at 9:00 a.m. both in fasting conditions and after a meal. The effect does not depend on the unusual time (8:00 a.m., selected for experimental needs) at which the subjects were given the meal. In fact, a 2.5-fold increase in plasma concentrations was observed when an oral dose of 0.75 g of diftalone was administered to 2 subjects (study II) both at 8:00 a.m. in fasting conditions and at 1:00 p.m. after a meal. A similar enhancement in the absorption of diftalone was observed when 5 healthy volunteers (study VI) received an oral dose of 0.5 g of the compound both as plain capsules and as capsules containing dry ox bile. However, the absorption of diftalone was not modified when the compound was administered orally as an aqueous suspension or in tensioactive vehicles, or after 20 mg of metoclopramide (study II). Also, the results of a study (IV) on 2 subjects partly deprived of bile after surgery, showed that diftalone does not undergo enterohepatic circulation. The hypothesis that the increase in diftalone absorption is mainly due to bile flow following food intake is supported by all the above experimental results.

Adult↗
PubMed1975

Isolation and structure determination of a further metabolite of diftalone.

A further metabolite of diftalone, a new antiinflammatory drug, has been identified as 7,14-dihydroxyphthalazino [2,3-b] phthalazine-5,12(7H,14H)-dione, on the basis of physico-chemical properties. The free metabolite was isolated from guinea-pig urine, where it is present as such and as the beta-glucuronide. This structure confirms the selective susceptibility of the methylene group of diftalone towards biological hydroxylation.

Animals↗